(SLC-001) Comparative Effectiveness of Injectable Versus Oral Pre-Exposure Prophylaxis (PrEP) for HIV Prevention

Background: The injectable long-acting cabotegravir (CAB-LA) was approved for HIV pre-exposure prophylaxis (PrEP) in 2021. Clinical trials have shown the efficacy of CAB-LA among men who have sex with men, transgender women and women at risk of HIV compared to oral PrEP, which has been used for a decade. Real-world evidence on its comparative effectiveness is limited.

Objectives: To assess the comparative effectiveness of CAB-LA versus oral PrEP in preventing HIV infection.

Methods: We conducted a retrospective cohort study using Merative MarketScan database (2019-2023). We included individuals aged ≥12 years who were prescribed either CAB-LA or oral PrEP regimens and had 12 months of continuous enrollment prior PrEP initiation. Oral PrEP was defined as 30 days supply of tenofovir-disoproxil-fumarate/emtricitabine or tenofovir-alafenamide/emtricitabine. We excluded individuals with diagnostic codes or prescriptions for HIV or hepatitis B virus during the 1-year baseline period prior to PrEP initiation. The outcome was HIV acquisition, identified using ICD-10-CM codes based on at least one inpatient or two outpatient claims. Censoring occurred at medication discontinuation (with a grace period of 63 days), loss of continuous enrollment, switching between treatment groups, or end of the study period, whichever came first. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates (e.g., sex, age, region, relevant comorbidities, sexual transmitted infection and HIV testing. A Cox proportional hazards model was used to estimate incident HIV infection hazard ratio (HR) and 95% confidence interval (CI). We conducted an intention-to-treat (ITT) analysis as a sensitivity analysis.

Results: Our study included 10,751 PrEP users: 126 (1.2%) were prescribed CAB-LA (87.3% male, mean age±SD: 37.7±11.8 years), and 10,625 (98.8%) received oral PrEP (96.3% male, 35.2 ±11.7 years). After IPTW, both treatment groups were well-balanced during the baseline period, with standardized mean differences < 0.1. We observed 1 new HIV cases among CAB-LA users and 182 cases among oral PrEP users. The incidence rates were 14.20 and 18.85 per 1000 person-years for CAB-LA and oral PrEP, respectively. In the Cox proportional hazards model, CAB-LA users were associated with an increased risk of new HIV infection compared to oral PrEP users (HR: 1.29, 95%CI: 1.03-1.62). Findings were consistent in the ITT analysis (HR: 2.06, 95%CI: 1.62-2.62).

Conclusions: Our findings suggest that CAB-LA may be associated with an increased risk of HIV acquisition compared to oral PrEP. However, caution is needed in interpreting these results due to the limited number of events and short follow-up period. Further studies with extended follow-up in real-world PrEP cohorts are needed.